Statistical Analysis of Molecular Signal Recording

A molecular device that records time-varying signals would enable new approaches in neuroscience. We have recently proposed such a device, termed a “molecular ticker tape”, in which an engineered DNA polymerase (DNAP) writes time-varying signals into DNA in the form of nucleotide misincorporation patterns. Here, we define a theoretical framework quantifying the expected capabilities of molecular ticker tapes as a function of experimental parameters. We present a decoding algorithm for estimating time-dependent input signals, and DNAP kinetic parameters, directly from misincorporation rates as determined by sequencing. We explore the requirements for accurate signal decoding, particularly the constraints on (1) the polymerase biochemical parameters, and (2) the amplitude, temporal resolution, and duration of the time-varying input signals. Our results suggest that molecular recording devices with kinetic properties similar to natural polymerases could be used to perform experiments in which neural activity is compared across several experimental conditions, and that devices engineered by combining favorable biochemical properties from multiple known polymerases could potentially measure faster phenomena such as slow synchronization of neuronal oscillations. Sophisticated engineering of DNAPs is likely required to achieve molecular recording of neuronal activity with single-spike temporal resolution over experimentally relevant timescales.United States. Defense Advanced Research Projects Agency. Living Foundries ProgramGoogle (Firm)New York Stem Cell Foundation. Robertson Neuroscience Investigator AwardNational Institutes of Health (U.S.) (EUREKA Award 1R01NS075421)National Institutes of Health (U.S.) (Transformative R01 1R01GM104948)National Institutes of Health (U.S.) (Single Cell Grant 1 R01 EY023173)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Science Foundation (U.S.) (CAREER Award CBET 1053233)National Science Foundation (U.S.) (Grant EFRI0835878)National Science Foundation (U.S.) (Grant DMS1042134)Paul G. Allen Family Foundation (Distinguished Investigator in Neuroscience Award

A novel emergency department based prevention intervention program for people living with HIV: evaluation of early experiences

<p>Abstract</p> <p>Background</p> <p>HIV prevention is increasingly focused on people living with HIV (PLWH) and the role of healthcare settings in prevention. Emergency Departments (EDs) frequently care for PLWH, but do not typically endorse a prevention mission. We conducted a pilot exploratory evaluation of the first reported ED program to address the prevention needs of PLWH.</p> <p>Methods</p> <p>This retrospective observational cohort evaluation reviewed program records to describe the first six months of participants and programmatic operation. Trained counselors provided a risk assessment and counseling intervention combined with three linkage interventions: i) linkage to health care, ii) linkage to case management, and iii) linkage to partner counseling and referral.</p> <p>Results</p> <p>Of 81 self-identified PLWH who were approached, 55 initially agreed to participate. Of those completing risk assessment, 17/53 (32%, 95 CI 20% to 46%) reported unprotected anal/vaginal intercourse or needle sharing in the past six months with a partner presumed to be HIV negative. Counseling was provided to 52/53 (98%). For those requesting services, 11/15 (73%) were linked to healthcare, 4/23 (17%) were coordinated with case management, and 1/4 (25%) completed partner counseling and referral.</p> <p>Conclusion</p> <p>Given base resources of trained counselors, it was feasible to implement a program to address the prevention needs for persons living with HIV in an urban ED. ED patients with HIV often have unmet needs which might be addressed by improved linkage with existing community resources. Healthcare and prevention barriers for PLWH may be attenuated if EDs were to incorporate CDC recommended prevention measures for healthcare providers.</p

Identification of Hammerhead Ribozymes in All Domains of Life Reveals Novel Structural Variations

Hammerhead ribozymes are small self-cleaving RNAs that promote strand scission by internal phosphoester transfer. Comparative sequence analysis was used to identify numerous additional representatives of this ribozyme class than were previously known, including the first representatives in fungi and archaea. Moreover, we have uncovered the first natural examples of “type II” hammerheads, and our findings reveal that this permuted form occurs in bacteria as frequently as type I and III architectures. We also identified a commonly occurring pseudoknot that forms a tertiary interaction critical for high-speed ribozyme activity. Genomic contexts of many hammerhead ribozymes indicate that they perform biological functions different from their known role in generating unit-length RNA transcripts of multimeric viroid and satellite virus genomes. In rare instances, nucleotide variation occurs at positions within the catalytic core that are otherwise strictly conserved, suggesting that core mutations are occasionally tolerated or preferred

Partner notification for sexually transmitted infections in developing countries: a systematic review

<p>Abstract</p> <p>Background</p> <p>The feasibility and acceptability of partner notification (PN) for sexually transmitted infections (STIs) in developing countries was assessed through a comprehensive literature review, to help identify future intervention needs.</p> <p>Methods</p> <p>The Medline, Embase, and Google Scholar databases were searched to identify studies published between January 1995 and December 2007 on STI PN in developing countries. A systematic review of the research extracted information on: (1) willingness of index patients to notify partners; (2) the proportion of partners notified or referred; (3) client-reported barriers in notifying partners; (4) infrastructure barriers in notifying partners; and (5) PN approaches that were evaluated in developing countries.</p> <p>Results</p> <p>Out of 609 screened articles, 39 met our criteria. PN outcome varied widely and was implemented more often for spousal partners than for casual or commercial partners. Reported barriers included sociocultural factors such as stigma, fear of abuse for having an STI, and infrastructural factors related to the limited number of STD clinics, and trained providers and reliable diagnostic methods. Client-oriented counselling was found to be effective in improving partner referral outcomes.</p> <p>Conclusions</p> <p>STD clinics can improve PN with client-oriented counselling, which should help clients to overcome perceived barriers. The authors speculate that well-designed PN interventions to evaluate the impact on STI prevalence and incidence along with cost-effectiveness components will motivate policy makers in developing countries to allocate more resources towards STI management.</p

Salicornia ramosissima population dynamics and tolerance of salinity

Abstract Field and greenhouse studies have been conducted to clarify aspects of population dynamics and NaCl tolerance of Salicornia ramosissima J. Woods. Two populations, Varela and Verdemilho, were monitored in the field during two consecutive life cycles and aspects of their morphology and density were recorded monthly. In the laboratory seedlings were exposed to different salinity for 10 weeks and growth and mortality rate were recorded weekly. The growth of the populations differed significantly, possibly because of the different salinities of the two sampling sites and/or genetic adaptations of the two populations to the environmental conditions. The absence of a significant correlation between sediment salinity and stem elongation suggested, however, that salinity, alone was not responsible for the differences observed and was possibly associated with other factors, because of nutritional, edaphic, and microclimatic conditions. S. ramosissima did not develop well in conditions of elevated or moderate salinity; its growth was optimum at low salinity. Optimum development of S. ramosissima may, nevertheless, depend on the total number of large seeds in a population seed bank, because of their greater success in germination and germinability under stress conditions than small seeds

Consequences of resource competition for sex allocation and discriminative behaviors in a hyperparasitoid wasp

[KEYWORDS: Reproduction Local mate competition Local resource competition Sex ratio Parasitoid Gelis acororum] Population-wide mating patterns can select for equal parental investment in both sexes, but limiting resources, such as mates or developmental substrates, can increase competition leading to biased sex ratios in favor of either sex. Such competition for resources typically occurs in spatially structured populations, where dispersal is limited. In this laboratory study, we investigate if and how resource competition affects sex allocation, discriminative behaviors and competitive interactions of the wingless hyperparasitoid Gelis acororum, which exploits patchily distributed hosts. We show that G. acororum sex ratios are male-biased and that this is not a consequence of constrained reproduction by virgin females. Our results suggest that this pattern of reproductive investment, which is only rarely observed in parasitoids, is a consequence of resource limitation, in terms of hosts rather than mates. Further, G. acororum appears not to respond to intrinsic host quality or to prior oviposition in its host. When competing inter-specifically for host resources, G. acororum outcompetes its congener Gelis agilis, but does so mainly when ovipositing on the host first. Overall, our results suggest that host resource limitation could be an important environmental factor shaping sex allocation in G. acororum, with competition taking place both intra- and inter-specifically.

Predictors of Partner Notification for C. trachomatis and N. gonorrhoeae: An Examination of Social Cognitive and Psychological Factors

Efforts to control chlamydial and gonococcal infections include notifying eligible sexual partners of possible infection, primarily by asking the diagnosed patient to notify their partners. This approach, known as patient referral, is widely used but poorly understood. The current study examined psychosocial and cognitive factors associated with patient referral among an urban, minority sample of 168 participants recently diagnosed with Chlamydia trachomatis or Neisseria gonorrhoeae. At a follow-up interview 1-month from diagnosis, participants were more likely to have notified all eligible partners if they had greater intention to notify at baseline (OR = 3.72; 95% CI = 1.34, 10.30) and if they had only one partner at baseline (OR = 4.08; 95% CI = 1.61, 10.31). There were also gender differences as well as differences based on type of partner (i.e., regular, casual, one-time). The implications of these findings for the design of programs to promote patient referral for sexually transmitted infections are discussed